This invention relates to ophthalmic compositions and methods for preserving and using such compositions. More particularly, the present invention relates to ophthalmic compositions, e.g., useful in caring for contact lenses, which include one or more of certain ionene polymers as preservatives or disinfectants, and to methods for disinfecting and/or preserving using such compositions.
Various compositions, e.g., solutions, are used in association with contact lenses to ensure that the lenses may be safely, comfortably and conveniently worn. Contact lens care compositions, for example, disinfecting compositions, preserving compositions, cleaning compositions, wetting compositions, conditioning compositions and the like, often utilize at least one disinfectant or preservative, depending on the type of composition, for disinfecting or preserving contact lenses after wear or preserving the lens care composition itself. A contact lens disinfecting composition generally has sufficient antimicrobial activity so that when the composition is contacted with a lens to be disinfected, microorganisms associated with the lens are killed or otherwise removed and the contact lens is effectively disinfected within a reasonable time, e.g., in the range of about 0.1 hour to about 12 hours. A contact lens disinfecting composition may be termed a microbicidal composition. In contrast, a contact lens preserving composition has sufficient antimicrobial activity, often less of such activity than is present in a contact lens disinfecting composition, so that when the composition is contacted with a contact lens substantially no increase in the microorganism population in the composition is obtained. A contact lens preserving composition may be termed a microbiostatic composition or a microbicidal composition. Contact lens care compositions are preserved to prevent any substantial increase in the population of contaminating microorganisms in the compositions and, thereby, to extend their shelf life. Such preserved contact lens care compositions may be termed microbiostatic compositions. Some preservatives used in lens preserving compositions or in preserved compositions may also be used as disinfecting agents in lens disinfecting compositions.
Various compounds are known for use as preserving agents in contacts lens preserving compositions and preserved contact lens care compositions. Examples include thimerosal, benzalkonium chloride and chlorhexidine. However, these preserving agents are known to exhibit ocular toxicity which may result in irritation or sensitivity to the eye. The degree of ocular toxicity increases when these agents are utilized as disinfecting agents. Further, a soft contact lens, a rigid gas permeable contact lens (RGP) or a hard contact lens can absorb or adsorb these compounds. This causes the contact lens to retain the irritating compound and contributes to the eye irritation and sensitivity which may result.
Stark U.S. Pat. No. 4,525,346 discloses a contact lens disinfecting solution and preserved contact lens care compositions containing 1-tris (2-hydroxyethyl) ammonium-2-butenyl-4-poly [1-dimethyl ammonium-2-butenyl]-w-tris (2-hydroxyethyl-) ammonium the salt of which has a pharmaceutically acceptable anion. The quaternary ammonium polymer disclosed in this Stark patent is capable of causing irritation and sensitivity to some contact lens wearers.
Japanese Patent Publication 63131124 discloses a liquid composition for contact lens care including as an antimicrobial component a polymeric condensate of a diamine, such as N,N,N',N'-tetramethyl 1,2-diaminoethane, and a dihalogen compound, such as 1,2-dichloroethane. Such polymeric condensates include no oxygen. Further, there is no suggestion that other polymeric condensates are useful as antimicrobial agents in the contact lens care context.
Other conventional methods of contact lens chemical disinfection utilize one or more active disinfecting agents in an aqueous medium, for example a chlorhexidine/thimerosal solution or a relatively mild solution of hydrogen peroxide. Some of these disinfecting solutions, such as those named above, are cytotoxic and are known to be adsorbed or absorbed onto or into a contact lens and cause the lens to elicit a cytotoxic response after disinfection. For example, contact lenses which have been soaked in a disinfecting hydrogen peroxide solution are to be treated to remove residual hydrogen peroxide, e.g., by soaking in a catalase solution, before they may be comfortably and safely worn again. If residual hydrogen peroxide remains on the lenses, then irritation or injury to the eye may result. A lens disinfecting system employing a substantially non-oxidative disinfectant composition is particularly useful since the risk of introducing active oxidizing agents into the eye is substantially eliminated.
Ellis et al U.S. Pat. No. 4,168,112 discloses treating an ionically charged contact lens with a lens solution containing an oppositely charged ionic polymer to form a hydrophilic polyelectrolyte complex on the lens surface. This complex forms a hydrogel and acts as a cushion which provides comfort to the eye. Ionene polymers are among the many ionic polymers disclosed by Ellis et al. In addition, Ellis et al discloses that other additives, such as preservatives, e.g., benzalkonium chloride, ethylenediaminetetraacetic acid, mercurials and chlorobutanol, can be included in the lens treating solutions. Ellis et al does not distinguish between ionene polymers, nor is there any suggestion than any ionene polymers are useful as preservatives or disinfectants in the contact lens care context.
Stockel et al U.S. Pat. No. 4,499,077 discloses oxidative contact lens disinfecting compositions including stabilized chlorine dioxide and a quaternary ammonium compound which is a copolymer of at least one mono-or di-tertiary amine and a dihalo organic compound. Stockel U.S. Pat. No. 4,654,208 discloses oxidative contact lens disinfecting compositions including one or more of the quaternary ammonium copolymers noted above in this paragraph plus a potentiating amount of an oxidizing agent. Neither of the Stockel et al patents disclose non-oxidative contact lens care compositions using such quaternary ammonium copolymers.
A number of patents have disclosed the use of 2-(thiocyanomethylthio)benzothiazole, alone or in combination with various other materials, as having antimicrobial activity in metalworking fluids (Hollis et al U.S. Pat. No. 5,198,440 and Hollis et al U.S. Pat. No. 5,196,443); as microbicidal preservatives for dyes, pastes, lumber, leather, textiles, pulp and industrial raw materials (Ito U.S. Pat. No. 4,866,081 and Ito et al U.S. Pat. No. 4,839,373); to control fouling by marine and fresh water mollusks (Hollis et al U.S. Pat. No. 4,866,080); and to inhibit growth of microorganisms in water used for industrial purposes (Buckman et al U.S. Pat. No. 4,293,559, Johnson et al U.S. Pat. No. 4,285,765 and Buckman et al U.S. Pat. No. 3,520,976). None of these patents, nor any known prior art, teach or suggest the use of benzothiazole derivatives in contact lens care compositions or in ophthalmic compositions. In fact, as noted above, benzothiazole derivatives have been suggested for use in heavy industrial applications which tends to lead away from using such materials in applications involving the eye, one of the most sensitive organs of the body.
In general, it is advantageous to reduce the amount of disinfectant and/or preservative used in the contact lens care context. For example, with reduced amounts of such materials present, adverse reactions to the compositions are reduced. Also, the cost of obtaining effective contact lens disinfection and preserved ophthalmic compositions is reduced.
Thus, it is readily apparent that a continuing need exists for safe and efficacious compositions that can be used as contact lens disinfecting and preserving compositions and as preserved contact lens care compositions.